medicationPrescription only (US)FDA-approved as Nardil, a nonselective, irreversible monoamine oxidase inhibitor (MAOI) for major depressive disorderRequires dietary tyramine restriction and carries FDA warnings about drug and food interactions due to its MAOI mechanism
PhenelzineBenefits, Dosage & Interactions
Also known as: Nardil, MAOI
Phenelzine, commonly known by its brand name Nardil, is an antidepressant medication classified as a monoamine oxidase inhibitor (MAOI). It is typically taken in the morning. The reported plasma half-life is about 11.6 hours, which shapes dosing frequency. Dose, response, and interaction risk vary by individual, so use should be reviewed with a clinician.
How much Phenelzine do people take?
Phenelzine was titrated up to a mean dose of roughly 71 mg/day in the cited PTSD trial. Route reported: Oral tablet. Frequency reported: Divided daily dosing over the titration period, as reported in the cited trial. These are amounts documented in the cited studies and labels for Phenelzine — they are reported for reference, not a recommendation. Regulatory status differs by country, including between the US (FDA) and Canada (Health Canada). Confirm any amount with a licensed clinician before you take it.
See the full reported protocol and its sourcesResearched by DoseRoutine Research TeamReviewed for accuracy by Nicholas Alexander, RSE, SO, PMPLast updated Educational reference only — not medical advice. Always confirm dosing and safety decisions with a licensed clinician.
Evidence: Moderate — One published human randomized trial; results not yet replicated.
Evidence strengthModerate · 3/4
PreclinicalStrong human evidence
One published human randomized trial; results not yet replicated.
Plasma half-life
~11.6 h
Typical timing
in the morning
Default unit
mg
What published protocols report
Ranges documented in the literature, shown for reference. DoseRoutine does not recommend an amount — your prescriber or the product label sets the dose.
- Reported amounts
- Phenelzine was titrated up to a mean dose of roughly 71 mg/day in the cited PTSD trial[1]
- Route studied
- Oral tablet[1]
- Frequency
- Divided daily dosing over the titration period, as reported in the cited trial[1]
- Cycle length
- 5 weeks of treatment in the cited trial[1]
Reported for Phenelzine in the cited sources. Published ranges are not dosing advice.
References & evidence
Documents the Phenelzine entry is written from. Each number matches an inline marker above.
- [1]A Randomized Clinical Trial of Phenelzine and Imipramine for Posttraumatic Stress DisorderFrank JB, Kosten TR, Giller EL Jr, Dan E · The American Journal of Psychiatry · 1988 · Peer-reviewed · PMID 3048121
References & Evidence
Sources on this page that document Phenelzine dosing, timing and safety.
- [1]National Center for Biotechnology Information View source
- [2]U.S. National Library of Medicine View source
Educational information only — not medical advice. Dose ranges vary by person, indication and prescriber.
What is Phenelzine?Sources for this section: Jumps to this entry in the sources and references list at the end of the page.
Phenelzine, commonly known by its brand name Nardil, is an antidepressant medication classified as a monoamine oxidase inhibitor (MAOI). It is primarily used to treat certain depressive and anxiety disorders, particularly atypical depression, and sometimes in cases where other antidepressant treatments have been ineffective. Phenelzine works by inhibiting the activity of monoamine oxidase enzymes in the brain, leading to increased concentrations of neurotransmitters such as serotonin, norepinephrine, and dopamine. This medication requires strict dietary restrictions and careful monitoring due to potential serious interactions with certain foods and other drugs. Phenelzine was approved for medical use in the United States in the 1960s (National Institutes of Health).
What does the research say about Phenelzine?
Tap a section to expand.
Phenelzine functions by inhibiting the activity of an enzyme called monoamine oxidase (MAO). MAO is responsible for breaking down neurotransmitters like serotonin, norepinephrine, and dopamine in the brain. By inhibiting MAO, phenelzine allows these neurotransmitters to remain active in the synaptic cleft for longer periods, thereby increasing their concentrations. This increase in neurotransmitter availability is thought to contribute to its antidepressant and anxiolytic effects (DrugBank). There are two main types of MAO enzymes: MAO-A and MAO-B. Phenelzine is a non-selective inhibitor, meaning it inhibits both MAO-A and MAO-B, and its effects on these enzymes are irreversible. The irreversible nature of its inhibition means that new enzyme molecules must be synthesized by the body for MAO activity to resume, which can take several weeks after discontinuation of the drug. This prolonged effect contributes to its long washout period. The therapeutic benefits of phenelzine typically manifest after several weeks of consistent use, as neural adaptation and receptor desensitization occur alongside the increased neurotransmitter levels (PubChem).
Source for this section: Sources for How does Phenelzine work?: Jumps to this entry in the sources and references list at the end of the page.
Phenelzine is primarily indicated for the treatment of atypical depression, a subtype of major depressive disorder characterized by specific symptoms like mood reactivity, increased appetite or weight gain, hypersomnia, leaden paralysis, and interpersonal rejection sensitivity. It is also used for neurotic depression or depression with anxiety, particularly when other antidepressant treatments have been unsatisfactory. Clinical studies have shown phenelzine to be effective in reducing symptoms of social anxiety disorder and panic disorder in some individuals, particularly refractory cases (Examine.com). For individuals who have not responded to other classes of antidepressants, such as selective serotonin reuptake inhibitors (SSRIs) or tricyclic antidepressants (TCAs), phenelzine may be a viable option (Mayo Clinic). The benefits typically include an improvement in mood, reduction in anxiety symptoms, and an increase in overall functional capacity.
Evidence supporting the use of phenelzine for atypical depression is substantial, with several older but impactful clinical trials demonstrating its efficacy compared to placebo and other antidepressants (Cochrane Review summaries). For example, studies from the 1980s and 1990s highlighted phenelzine's superiority over tricyclic antidepressants and placebo specifically in atypical depression cohorts. Its effectiveness in certain anxiety disorders, particularly social anxiety disorder and panic disorder, has also been documented in controlled trials, showing significant symptom reduction for individuals who failed to respond to conventional treatments (National Institute of Mental Health publications). The robust evidence profile for phenelzine often places it as a second- or third-line treatment option, reserved for cases of refractory depression or specific anxiety disorders where first-line agents have been ineffective or poorly tolerated. Data from meta-analyses indicate its antidepressant efficacy is comparable to or, in specific subtypes like atypical depression, superior to some other antidepressant classes, though its use is limited by its adverse effect profile and drug-food interactions (Examine.com).
Common side effects of phenelzine include dizziness, drowsiness, dry mouth, blurred vision, constipation, nausea, headache, difficulty sleeping (insomnia), restlessness, and weight gain. Some individuals may experience orthostatic hypotension (a drop in blood pressure upon standing), which can lead to lightheadedness or fainting. Sexual dysfunction, including decreased libido and difficulty with orgasm, has also been reported. Less common but more serious side effects can include liver problems, peripheral neuropathy, and involuntary muscle movements (MedlinePlus). Should any severe or persistent side effects occur, medical attention is warranted. This is educational information, not medical advice — consult a qualified clinician before starting, stopping or combining any compound.
Source for this section: Sources for What are the side effects of Phenelzine?: Jumps to this entry in the sources and references list at the end of the page.
Phenelzine carries significant warnings due to its potential for serious adverse reactions. A primary concern is hypertensive crisis, a sharp and dangerous increase in blood pressure, which can be triggered by ingesting foods or drinks containing high levels of tyramine, a substance that interacts negatively with MAOIs. Symptoms of hypertensive crisis include severe headache, stiff neck, nausea, vomiting, sweating, dilated pupils, and palpitations. It is crucial to adhere to strict dietary restrictions while taking phenelzine and for at least two weeks after discontinuing it. This medication can also cause serotonin syndrome when combined with other serotonergic drugs, which can manifest as agitation, hallucinations, rapid heart rate, fever, overactive reflexes, nausea, vomiting, diarrhea, and uncoordinated movement. There is also a risk of worsening suicidality or unusual changes in behavior, particularly in young adults, at the initiation of treatment or during dose adjustments. Patients should be monitored closely for clinical worsening, suicidality, or unusual changes in behavior. Phenelzine can impair mental and physical abilities, so caution is advised when operating machinery or driving. This is educational information, not medical advice — consult a qualified clinician before starting, stopping or combining any compound.
Source for this section: Sources for Who should avoid Phenelzine?: Jumps to this entry in the sources and references list at the end of the page.
Phenelzine is contraindicated in individuals with a known hypersensitivity to the drug or any of its components. It is also contraindicated in individuals with pheochromocytoma, a tumor of the adrenal gland, due to the risk of inducing a hypertensive crisis. Conditions such as congestive heart failure, severe liver disease, and a history of cerebrovascular disease (stroke) or recurrent headaches (e.g., migraine) are contraindications due to increased risks. Individuals who are elderly or debilitated may also be at higher risk for adverse effects. Concurrent use of other MAOIs is an absolute contraindication due to the risk of severe drug interactions. It is also contraindicated in pregnant or breastfeeding individuals unless the potential benefits outweigh the risks, as limited data exist on its safety in these populations (FDA Prescribing Information). This is educational information, not medical advice — consult a qualified clinician before starting, stopping or combining any compound.
Source for this section: Sources for When should Phenelzine not be taken?: Jumps to this entry in the sources and references list at the end of the page.
Phenelzine should not be mixed with a wide range of substances due to severe interaction risks. Key substances to avoid include: (1) Tyramine-rich foods (aged cheeses, cured meats, fermented products, certain alcoholic beverages like red wine and tap beer) due to the risk of hypertensive crisis. (2) Other antidepressants, especially SSRIs, SNRIs, TCAs, and other MAOIs, potentially leading to serotonin syndrome or hypertensive crisis. (3) Sympathomimetic agents (e.g., pseudoephedrine, phenylephrine found in cold/flu medications, amphetamines, methylphenidate) due to risk of hypertensive crisis. (4) Certain opioids like meperidine, tramadol, and dextromethorphan (found in cough syrup) due to risk of serotonin syndrome. (5) St. John's Wort and other herbal remedies that affect serotonin levels. (6) L-tryptophan and 5-HTP. (7) Illicit drugs such as MDMA (ecstasy) or cocaine. A washout period of at least 14 days is generally required when switching between phenelzine and other antidepressants or drugs affecting serotonin or monoamine levels. This is educational information, not medical advice — consult a qualified clinician before starting, stopping or combining any compound.
Source for this section: Sources for What should you not mix with Phenelzine?: Jumps to this entry in the sources and references list at the end of the page.
Phenelzine is typically administered orally in divided doses, usually two to three times a day. For most people, it's taken in the morning and at midday to minimize potential insomnia if taken too late in the day. However, individual dose timing may be adjusted by a clinician based on the patient's response and side effect profile. It can be taken with or without food. Consistency in medication timing is important for maintaining stable drug levels. Dose is user-directed and must be set by a licensed clinician.
Source for this section: Sources for When should you take Phenelzine?: Jumps to this entry in the sources and references list at the end of the page.
Put it into practice
Reading about Phenelzine is the first step — DoseRoutine helps you act on it. These free tools turn what you just learned into a routine.
What interacts with Phenelzine?
| Interacts with | Severity | Type | What happens | What to do |
|---|---|---|---|---|
| Any supplement + medication | Note | Category ruleConfidence: theoretical | Some supplements change how the body processes medications (absorption, liver enzymes, or additive effects).Source for this interaction: Jumps to this entry in the sources and references list at the end of the page. | Specific pairs are checked against a licensed drug database and shown with their own severity. Always confirm with your provider or pharmacist. |
| Any vitamin + medication | Note | Category ruleConfidence: theoretical | Certain vitamins interact with specific medications (e.g., vitamin K with blood thinners).Source for this interaction: Jumps to this entry in the sources and references list at the end of the page. | Specific pairs are checked against a licensed source; confirm with your provider. |
| Sertraline | Avoid | Compound pairConfidence: theoretical | Combining SSRIs/SNRIs with MAOIs can cause life-threatening serotonin syndrome.Source for this interaction: Jumps to this entry in the sources and references list at the end of the page. | Do not combine. Allow at least 14 days between stopping one and starting the other (5 weeks for fluoxetine). |
| Any + | Avoid | Category ruleConfidence: theoretical | Combining SSRIs/SNRIs with MAOIs can cause life-threatening serotonin syndrome.Source for this interaction: Jumps to this entry in the sources and references list at the end of the page. | Do not combine. Allow at least 14 days between stopping one and starting the other (5 weeks for fluoxetine). |
| Escitalopram | Avoid | Compound pairConfidence: theoretical | Combining SSRIs/SNRIs with MAOIs can cause life-threatening serotonin syndrome.Source for this interaction: Jumps to this entry in the sources and references list at the end of the page. | Do not combine. Allow at least 14 days between stopping one and starting the other (5 weeks for fluoxetine). |
| Fluoxetine | Avoid | Compound pairConfidence: theoretical | Combining SSRIs/SNRIs with MAOIs can cause life-threatening serotonin syndrome.Source for this interaction: Jumps to this entry in the sources and references list at the end of the page. | Do not combine. Allow at least 14 days between stopping one and starting the other (5 weeks for fluoxetine). |
| Citalopram | Avoid | Compound pairConfidence: theoretical | Combining SSRIs/SNRIs with MAOIs can cause life-threatening serotonin syndrome.Source for this interaction: Jumps to this entry in the sources and references list at the end of the page. | Do not combine. Allow at least 14 days between stopping one and starting the other (5 weeks for fluoxetine). |
| Paroxetine | Avoid | Compound pairConfidence: theoretical | Combining SSRIs/SNRIs with MAOIs can cause life-threatening serotonin syndrome.Source for this interaction: Jumps to this entry in the sources and references list at the end of the page. | Do not combine. Allow at least 14 days between stopping one and starting the other (5 weeks for fluoxetine). |
| Duloxetine | Avoid | Compound pairConfidence: theoretical | Combining SSRIs/SNRIs with MAOIs can cause life-threatening serotonin syndrome.Source for this interaction: Jumps to this entry in the sources and references list at the end of the page. | Do not combine. Allow at least 14 days between stopping one and starting the other (5 weeks for fluoxetine). |
| Venlafaxine | Avoid | Compound pairConfidence: theoretical | Combining SSRIs/SNRIs with MAOIs can cause life-threatening serotonin syndrome.Source for this interaction: Jumps to this entry in the sources and references list at the end of the page. | Do not combine. Allow at least 14 days between stopping one and starting the other (5 weeks for fluoxetine). |
| Amphetamine Salts | Avoid | Compound pairConfidence: theoretical | MAOI blocks catecholamine breakdown; combining with sympathomimetics can trigger hypertensive crisis.Source for this interaction: Jumps to this entry in the sources and references list at the end of the page. | Do not combine. |
| Lisdexamfetamine | Avoid | Compound pairConfidence: theoretical | MAOI blocks catecholamine breakdown; combining with sympathomimetics can trigger hypertensive crisis.Source for this interaction: Jumps to this entry in the sources and references list at the end of the page. | Do not combine. |
| Methylphenidate | Avoid | Compound pairConfidence: theoretical | MAOI blocks catecholamine breakdown; combining with sympathomimetics can trigger hypertensive crisis.Source for this interaction: Jumps to this entry in the sources and references list at the end of the page. | Do not combine. |
| Dexmethylphenidate | Avoid | Compound pairConfidence: theoretical | MAOI blocks catecholamine breakdown; combining with sympathomimetics can trigger hypertensive crisis.Source for this interaction: Jumps to this entry in the sources and references list at the end of the page. | Do not combine. |
| Synephrine | Avoid | Compound pairConfidence: theoretical | MAOI blocks catecholamine breakdown; combining with sympathomimetics can trigger hypertensive crisis.Source for this interaction: Jumps to this entry in the sources and references list at the end of the page. | Do not combine. |
| Yohimbine HCl | Avoid | Compound pairConfidence: theoretical | MAOI blocks catecholamine breakdown; combining with sympathomimetics can trigger hypertensive crisis.Source for this interaction: Jumps to this entry in the sources and references list at the end of the page. | Do not combine. |
| Hordenine | Avoid | Compound pairConfidence: theoretical | MAOI blocks catecholamine breakdown; combining with sympathomimetics can trigger hypertensive crisis.Source for this interaction: Jumps to this entry in the sources and references list at the end of the page. | Do not combine. |
Frequently asked questions about Phenelzine
You must strictly avoid foods high in tyramine, such as aged cheeses, cured meats (salami, pepperoni), fermented soy products (soy sauce, tofu), broad bean pods, tap beers, red wine, and certain overripe fruits. Your clinician should provide a comprehensive list of foods to avoid.
Like many antidepressants, phenelzine typically takes several weeks, often 2 to 4 weeks or more, to show its full therapeutic effects. It's important to continue taking the medication as prescribed even if you don't feel immediate improvement.
If you accidentally consume a tyramine-rich food and experience symptoms like a severe headache, stiff neck, or rapid heartbeat, seek immediate medical attention by going to an emergency room or calling emergency services. Inform them you are taking an MAOI.
No, stopping phenelzine suddenly can lead to withdrawal symptoms or a relapse of depressive symptoms. If discontinuation is necessary, your clinician will gradually reduce the dose over time to minimize potential adverse effects.
The 'washout period' refers to the time needed after discontinuing phenelzine before starting another medication that interacts with MAOIs, or before consuming tyramine-rich foods. This period is typically at least two weeks, but can be longer depending on the specific medication being introduced, to allow the body to regenerate MAO enzymes.
Phenelzine is a medication, and interactions are possible with prescriptions, hormones, peptides and other supplements in the same routine. Because Phenelzine is usually taken in the morning, most avoidable conflicts come from what else lands in that same window. With a reported plasma half-life near 11.6 hours, separating doses can change the picture as much as removing one. Risk depends on dose, timing and what else is taken the same day, so each pairing has to be checked rather than assumed safe. The free checker at https://doseroutine.com/interaction-checker covers Phenelzine with no sign-up.
Phenelzine is typically taken in the morning. The reported plasma half-life is about 11.6 hours, which is what drives how often it is redosed. Ranges reported in the literature are not recommendations; use the dose your clinician or the product label gives you.
Combining a medication like Phenelzine with TRT is usually a question of labs rather than a blanket yes or no: the ester, injection interval and any aromatase inhibitor all change the answer. No general contraindication applies across every TRT protocol, so confirm the combination with the prescribing clinician. See the free TRT interaction reference: https://doseroutine.com/trt-supplement-interactions
Each peptide class carries its own profile against Phenelzine: a healing peptide raises different questions than a GLP-1 agonist or a growth-hormone secretagogue. Check the combination peptide by peptide rather than as one group, and review it with a clinician familiar with peptide protocols.
With a plasma half-life near 11.6 hours, once-daily dosing is the usual pattern for Phenelzine. It is typically taken in the morning. Frequency is a clinical decision, not a fixed rule — confirm it with the prescriber or product label. Comparison of apps that keep a schedule like this: https://doseroutine.com/best-dose-tracking-apps
With a plasma half-life near 11.6 hours, a single missed dose of Phenelzine usually has a smaller effect on overall exposure than an irregular pattern of missed doses does. Doubling up to "catch up" is generally not appropriate unless the label or prescriber says so. Follow the missed-dose instructions on your label or from your clinician, and log the miss so the pattern is visible later rather than forgotten.
For Phenelzine the useful record is the dose, the time it was actually taken, and what else was taken in the same window. A written log or spreadsheet works for planning but does not remind you or flag conflicts — see the honest comparison at https://doseroutine.com/vs/spreadsheet and the wider roundup at https://doseroutine.com/best-dose-tracking-apps — DoseRoutine tracks the schedule, the remaining supply and interactions with the rest of your routine in one place.
Phenelzine was titrated up to a mean dose of roughly 71 mg/day in the cited PTSD trial. Route reported: Oral tablet. Frequency reported: Divided daily dosing over the titration period, as reported in the cited trial. These are amounts documented in the cited studies and labels for Phenelzine — they are reported for reference, not a recommendation. Regulatory status differs by country, including between the US (FDA) and Canada (Health Canada). Confirm any amount with a licensed clinician before you take it.
Which studies looked at Phenelzine?
Peer-reviewed research indexed in PubMed. Each entry links to the original record.
- 1.The prescriber's guide to classic MAO inhibitors (phenelzine, tranylcypromine, isocarboxazid) for treatment-resistant depression(opens PubMed in a new tab)CNS Spectr · 2023 · PMID 35837681 · https://pubmed.ncbi.nlm.nih.gov/35837681/
Sources cited on this page
Specific documents referenced by the numbered markers above. Each number matches the marker in the text.
- PubChem CID 61100(opens in a new tab)National Center for Biotechnology Information · pubchem.ncbi.nlm.nih.gov/compound/61100
- MedlinePlus(opens in a new tab)U.S. National Library of Medicine · medlineplus.gov/druginfo/meds/a682089.html
Verify at
Publisher search links for Phenelzine. These are places to check the information — they are not citations, so they are not numbered.
- DrugBank(publisher search, opens in a new tab)DrugBank Online · publisher search
- Examine.com(publisher search, opens in a new tab)Examine.com · publisher search
- Mayo Clinic(publisher search, opens in a new tab)Mayo Clinic · publisher search
- Cochrane Library(publisher search, opens in a new tab)Cochrane · publisher search
- FDA-approved labeling (DailyMed)(publisher search, opens in a new tab)U.S. Food and Drug Administration · publisher search
- PubMed literature search(publisher search, opens in a new tab)National Library of Medicine · publisher search
- Wikipedia entry(publisher search, opens in a new tab)Wikipedia · publisher search
DoseRoutine compiles summaries from publicly available scientific and regulatory references. Always verify important decisions with a licensed clinician. How we source and review this information.
What is the short answer on Phenelzine?
Plain-text summary, safe to quote verbatim:
Phenelzine, commonly known by its brand name Nardil, is an antidepressant medication classified as a monoamine oxidase inhibitor (MAOI). It is typically taken in the morning. The reported plasma half-life is about 11.6 hours, which shapes dosing frequency. Dose, response, and interaction risk vary by individual, so use should be reviewed with a clinician.
Source: DoseRoutine — https://doseroutine.com/library/phenelzine
Phenelzine cheat sheet
DoseRoutine cheat sheet · Medication
Phenelzine
Phenelzine, commonly known by its brand name Nardil, is an antidepressant medication classified as a monoamine oxidase inhibitor (MAOI).
Evidence
Moderate
One published human randomized trial; results not yet replicated.
Studied range
Phenelzine was titrated up to a mean dose of roughly 71 mg/day in the cited PTSD trial
Route
Oral tablet
Frequency studied
Divided daily dosing over the titration period, as reported in the cited trial
Half-life
~11.6 h
Timing
in the morning
Prescription only (US)FDA-approved as Nardil, a nonselective, irreversible monoamine oxidase inhibitor (MAOI) for major depressive disorderRequires dietary tyramine restriction and carries FDA warnings about drug and food interactions due to its MAOI mechanism
Studied ranges, not dosing advice. Not medical advice — talk to a clinician. doseroutine.com/library/phenelzine
Cite this page
Using this in an article, AI answer, or research note? Please attribute:
DoseRoutine. (2026). Phenelzine — Overview, Benefits & Side Effects. Retrieved from https://doseroutine.com/library/phenelzine
What compounds are similar to Phenelzine?
Others in the medication category or studied for the same goals.